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The BTEX compounds (benzene, toluene, ethylbenzene, and xylenes) and formaldehyde (FA) have harmful impacts on human health and are also important precursors of tropospheric ozone and secondary organic aerosols (SOA). Thus, the objective of this study was to perform a human health risk assessment considering the lifetime carcinogenic (LCR) and non-carcinogenic (as hazard quotient (HQ)) risks for 3 different age groups associated with exposure to BTEX and FA by inhalation using a probabilistic approach with Monte Carlo simulation, as well as to evaluate the contributions of these compounds to ozone formation potential (OFP) and SOA formation potential (SOAFP), at seven sites in the city of Salvador, Bahia, Brazil, during the dry and rainy periods. The HQ values associated with BTEX and FA compounds were below the limit set by the USEPA (HQ = 1) for all groups in both periods. The LCR values for benzene and FA at the 95th percentile considering 3 evaluated groups were 2.49 × 10−6, 3.56 × 10−6, 9.16 × 10−6 and 1.83 × 10−5, 2.53 × 10−5, 6.55 × 10−5 in the dry period and 2.83 × 10−6, 3.94 × 10−6, 1.01 × 10−5 and 7.97 × 10−6, 1.02 × 10−5, 2.40 × 10−5 in the rainy period, respectively, being all values above the acceptable limit by the USEPA (1.0 × 10−6). For all 3 groups of the population, the LCR values for benzene and FA were higher during the rainy period and dry period, respectively, following the same pattern as the concentrations. FA, xylenes, and toluene accounted for up to 97.0% of total OFP, whereas toluene, benzene, and xylenes contributed up to 88.5% of total SOAFP. The results obtained showed the need to adopt measures to reduce BTEX and FA emissions in order to minimize the impacts on health of the exposed population and on air quality.

This work evaluated BTEX, HCHO, and CH3COH concentrations in the 5 most populated Brazilian urban centers. We investigated contributing sources in both dry and rainy periods, together with the ozone formation potential (OFP) and the possibly related health risk. Six simultaneous campaigns by passive sampling were carried out from August/2017 to June/2018, for periods of 14 days. The compounds were quantified by GC-FID (BTEX) and HPLC–UV/Vis (aldehydes). Atmospheric concentrations varied within 0.97 μg m−3 (m, p-xylene) to 28 μg m−3 (benzene). The HCHO and CH3COH concentration levels exceeded international recommendations in all the studied urban centers. Benzene concentrations were above 1.7 μg m−3, which is associated with a higher probability of individuals that may develop leukemia. Toluene/Benzene, Xylenes/Benzene, m,p-Xylene/Ethylbenzene, and Formaldehyde/Acetaldehyde ratios indicated vehicle emissions are the main sources of these volatile organic compounds. In addition, the Formaldehyde/Acetaldehyde ratios demonstrate the changes generated in the urban atmosphere of Brazilian cities due to the decrease in the consumption of ethanol fuel. Multivariate analysis separated two groups. CH3COH and benzene were the compounds that most contributed to the clustering of the São Paulo and Belo Horizonte centers, while HCHO, Toluene, Ethylbenzene, and xylenes contributed to the clustering of Salvador, Rio de Janeiro, and Londrina. The HQ data for the BTEX and aldehydes levels were below 1 (HQ < 1). Lifetime carcinogenic risk (LCR) values for HCHO and benzene due to exposure to the atmosphere were above the acceptable USEPA limit (1.0 × 10–6). HCHO, CH3COH, and toluene were the main contributors to the OFP.

Viscum album L., popularly known as mistletoe, is well known for its anti-cancer properties, and the pharmaceutical application of hydroalcoholic dry extracts is still limited due to its low solubility in aqueous media, and physicochemical instability. The Pluronic® F127 is an amphiphilic polymer, which permits the solubilization of lipophilic and hydrophilic compounds. In this investigation, physicochemical features of hydrogel containing V. album dry extract (VADE-loaded-hydrogel) were performed by: dynamic light scattering (DLS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). VADE-loaded-hydrogel presented nanometer-size micelles with volume distribution ranging from 10.58 nm to 246.7 nm, and a polydispersity index of 0.441. The sample thermal analyses (TG and DSC) showed similar decomposition curves; however, the thermal events indicated an increase in thermal stability in relation to the presence of the extract. In addition to these interesting pharmaceutical features, IC50 values of 333.40 µg/mL and >1000 µg/mL were obtained when tumor (SCC-25) and non-tumor (L929) cells were incubated with VADE-loaded-hydrogel, respectively. The optical and ultrastructural cellular analysis confirmed the tumor selectivity since the following alterations were detected only in SCC-25 cells: disorganization of plasmatic membrane; an increase of cytoplasmatic vacuole size; alteration in the cristae mitochondrial shape; and generation of amorphous cellular material. These results emphasize the promising antitumoral potential of VADE-loaded-hydrogel as an herbal drug delivery system via in vitro assays.

This study measures the curcumin concentration in rat plasma by liquid chromatography and investigates the changes in the glucose tolerance and insulin sensitivity of streptozotocin-diabetic rats treated with curcumin-enriched yoghurt. The analytical method for curcumin detection was linear from 10 to 500 ng/mL. The Cmax⁡ and the time to reach Cmax⁡ (tmax⁡) of curcumin in plasma were 3.14 ± 0.9 μg/mL and 5 minutes (10 mg/kg, i.v.) and 0.06 ± 0.01 μg/mL and 14 minutes (500 mg/kg, p.o.). The elimination half-time was 8.64 ± 2.31 ​​(i.v.) and 32.70 ± 12.92 (p.o.) minutes. The oral bioavailability was about 0.47%. Changes in the glucose tolerance and insulin sensitivity were investigated in four groups: normal and diabetic rats treated with yoghurt (NYOG and DYOG, resp.) and treated with 90 mg/kg/day curcumin incorporated in yoghurt (NC90 and DC90, resp.). After 15 days of treatment, the glucose tolerance and the insulin sensitivity were significantly improved in DC90 rats in comparison with DYOG, which can be associated with an increase in the AKT phosphorylation levels and GLUT4 translocation in skeletal muscles. These findings can explain, at least in part, the benefits of curcumin-enriched yoghurt to diabetes and substantiate evidences for the curcumin metabolite(s) as being responsible for the antidiabetic activity.

Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the subsp. (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract's chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed. subsp. histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS. The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks. This is the first histochemistry analysis of subsp. growing on . which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE.

Background Oxidative stress is a state in which excess reactive oxygen species (ROS) overwhelm endogenous antioxidant systems. It is known that this state has been involved in the development of hypertension. On the basis of previous data, we hypothesized that overactivity of NAD(P)H oxidase-derived ROS and the lowered activity of CuZnSOD, an endogenous antioxidant within the rostral ventrolateral medulla (RVLM), could contribute to 2K-1C (two-kidney one-clip) hypertension. Moreover, to test the functional significance of whether oxidative stress was involved in the maintenance of sympathetic vasomotor tone and blood pressure in 2K-1C hypertension, we administered Ascorbic Acid (Vit C), an antioxidant, into the RVLM or systemically. Methods Experiments were performed in male Wistar rats (6 weeks after renal surgery - Goldblatt hypertension model - 2K-1C). The mRNA expression of NAD(P)H oxidase subunits (p47phox and gp91phox) and CuZnSOD were analyzed in the RVLM using real-time PCR technique. The mean arterial blood pressure, heart rate, and renal sympathetic nerve activity were analyzed. Blood samples were collected and measured using thiobarbituric acid-reactive substances (TBARS). Results The mRNA expression of NAD(P)H oxidase subnits (p47phox and gp91pox) was greater in 2K-1C compared to the control group in the RVLM, and CuZnSOD expression was similar in both groups. In the RVLM, Vit C resulted in a fall in arterial pressure and in the sympathetic activity only in the 2K-1C rats. Thiobarbituric acid-reactive substances (TBARS) were significantly greater in 2K-1C rats and the acute infusion of Vit C significantly decreased arterial pressure and renal sympathetic activity in 2K-1C. Conclusions The results support the idea that an increase in oxidative stress within the RVLM and systemically plays a major role in maintaining high arterial blood pressure and sympathetic drive in 2K-1C hypertension.

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.

The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to stresses including UV- and ionizing-radiation, heat and desiccation, toxic metals, and organic pollutants. Consequently, they are amongst the most stunning extremophiles and poly-extreme-tolerant organisms on Earth. Even though ca. 60 black fungal genomes have been sequenced to date, [mostly in the family Herpotrichiellaceae (Eurotiomycetes)], the class Dothideomycetes that hosts the largest majority of extremophiles has only been sparsely sampled. By sequencing up to 92 species that will become reference genomes, the “Shed light in The daRk lineagES of the fungal tree of life” (STRES) project will cover a broad collection of black fungal diversity spread throughout the Fungal Tree of Life. Interestingly, the STRES project will focus on mostly unsampled genera that display different ecologies and life-styles (e.g., ant- and lichen-associated fungi, rock-inhabiting fungi, etc.). With a resequencing strategy of 10- to 15-fold depth coverage of up to ~550 strains, numerous new reference genomes will be established. To identify metabolites and functional processes, these new genomic resources will be enriched with metabolomics analyses coupled with transcriptomics experiments on selected species under various stress conditions (salinity, dryness, UV radiation, oligotrophy). The data acquired will serve as a reference and foundation for establishing an encyclopedic database for fungal metagenomics as well as the biology, evolution, and ecology of the fungi in extreme environments.

Non-ulcerated cutaneous leishmaniasis (NUCL) is an atypical clinical form of leishmaniasis first described, in 1988, by Ponce and collaborators, in Honduras, Central America, characterized by isolated or disseminated closed skin lesions appearing as papules, nodules, or infiltrated plaques, primarily in adolescents and young adults. Leishmania (L.) chagasi was then identified as the causal agent of both NUCL and American visceral leishmaniasis (AVL) in Honduras, though NUCL has been reported as more prevalent. However, due to the uncertain taxonomic classification of the NUCL-causing parasite, especially since L. (L.) chagasi has not been associated to this form of the disease in South America, this study conducted a comprehensive taxonomic review incorporating phenotypic (biological and clinical-immunopathological) and genotypic (genomic/molecular) analyses. Biologically, Honduran parasite-LPG does not have Gal (β1,4) Man (α1)-PO4 side chains common to all Leishmania LPGs. From a clinical-pathogenic perspective, NUCL is unique, it does not ulcerate like cutaneous leishmaniasis due to L. (L.) chagasi or L. (L.) infantum . Molecular findings showed that the Honduran parasite is more ancestral than all known viscerotropic Leishmania species, exhibited an unprecedented structural variation on chromosome 17 with the highest frequency of genomic SNPs, formed a distinct phylogenetic lineage, and displayed a homozygous SNP profile typical of a parental (non-hybrid) parasite. Building on these findings, a new species, Leishmania (Leishmania) poncei n. sp. (Kinetoplastea: Trypanosomatidae), is proposed in honor of Professor Carlos Ponce, who first described NUCL in Honduras. This study formally classifies L. (L.) poncei n. sp. as a novel Leishmania species responsible for both NUCL and AVL in Honduras, Central America.

Background Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The ‘Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard’ (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions. Methods In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs. Discussion The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care. Trial registration ISRCTN, ISRCTN24825698 . Registered 17/12/2020.